Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7
Purpose: To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point. Design: A modified Delphi study. Participants: Int...
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2025-09-01
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| author | Zhichao Wu, BAppSc(Optom), PhD Srinivas R. Sadda, MD Thomas Ach, MD Barbara A. Blodi, MD Ferdinando Bottoni, MD Usha Chakravarthy, MD, PhD Emily Y. Chew, MD Christine A. Curcio, PhD Frederick L. Ferris, III, MD Monika Fleckenstein, MD K. Bailey Freund, MD Juan E. Grunwald, MD Frank G. Holz, MD Glenn J. Jaffe, MD Sandra Liakopoulos, MD Tock Han Lim, FRCSEd Jordi M. Monés, MD, PhD Sergio Pagliarini, MD, FRCOphth Daniel Pauleikhoff, MD Maximilian Pfau, MD Philip J. Rosenfeld, MD, PhD David Sarraf, MD Steffen Schmitz-Valckenberg, MD Richard F. Spaide, MD Janet R. Sparrow, PhD Giovanni Staurenghi, MD Adnan Tufail, MD Francesco Viola, MD Robyn H. Guymer, MBBS, PhD |
| author_facet | Zhichao Wu, BAppSc(Optom), PhD Srinivas R. Sadda, MD Thomas Ach, MD Barbara A. Blodi, MD Ferdinando Bottoni, MD Usha Chakravarthy, MD, PhD Emily Y. Chew, MD Christine A. Curcio, PhD Frederick L. Ferris, III, MD Monika Fleckenstein, MD K. Bailey Freund, MD Juan E. Grunwald, MD Frank G. Holz, MD Glenn J. Jaffe, MD Sandra Liakopoulos, MD Tock Han Lim, FRCSEd Jordi M. Monés, MD, PhD Sergio Pagliarini, MD, FRCOphth Daniel Pauleikhoff, MD Maximilian Pfau, MD Philip J. Rosenfeld, MD, PhD David Sarraf, MD Steffen Schmitz-Valckenberg, MD Richard F. Spaide, MD Janet R. Sparrow, PhD Giovanni Staurenghi, MD Adnan Tufail, MD Francesco Viola, MD Robyn H. Guymer, MBBS, PhD |
| author_sort | Zhichao Wu, BAppSc(Optom), PhD |
| collection | DOAJ |
| description | Purpose: To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point. Design: A modified Delphi study. Participants: International panel of experts in AMD, retinal imaging, and histopathology that are part of the Classification of Atrophy Meetings group. Methods: A modified Delphi study was undertaken to determine if there is consensus on the acceptability of the onset of end-stage atrophic AMD as a clinical end point to evaluate early interventions and the criteria for defining such an end point. Two initial rounds of online surveys were conducted. Aggregate results and anonymized comments were provided after each round, followed by a face-to-face meeting before a final survey round was completed. Main Outcome Measures: Statements where consensus was reached, defined as ≥80% of responses within the 3-point bracket for agreement or disagreement based on a 9-point Likert rating scale, from a total of 33 statements included in the final round of the survey. Results: Consensus was reached for the statement that the onset of end-stage atrophic AMD was an appropriate clinical end point to evaluate early interventions (82% responses in agreement). Consensus was also reached for the statement that such an end point should be defined based on anatomical changes that have been previously shown in clinical studies to be associated with marked, but not necessarily complete, functional loss (95% responses in agreement). Consensus was nearly reached for the specific criterion that ≥90% of such atrophic AMD lesions should have ≥1 test location that was ≤10 decibels on 2 microperimetry tests (77% responses in agreement). Conclusions: There was expert group consensus that the onset of end-stage atrophy is an appropriate clinical end point to evaluate early interventions in AMD, and that such an end point should show evidence of marked functional loss in prior clinical studies. We believe these findings will help to define incident clinical end points that are acceptable to regulatory authorities. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. |
| format | Article |
| id | doaj-art-7f8553d3618448aebb777f92e0effadd |
| institution | OA Journals |
| issn | 2666-9145 |
| language | English |
| publishDate | 2025-09-01 |
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| series | Ophthalmology Science |
| spelling | doaj-art-7f8553d3618448aebb777f92e0effadd2025-08-20T02:16:18ZengElsevierOphthalmology Science2666-91452025-09-015510077710.1016/j.xops.2025.100777Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7Zhichao Wu, BAppSc(Optom), PhD0Srinivas R. Sadda, MD1Thomas Ach, MD2Barbara A. Blodi, MD3Ferdinando Bottoni, MD4Usha Chakravarthy, MD, PhD5Emily Y. Chew, MD6Christine A. Curcio, PhD7Frederick L. Ferris, III, MD8Monika Fleckenstein, MD9K. Bailey Freund, MD10Juan E. Grunwald, MD11Frank G. Holz, MD12Glenn J. Jaffe, MD13Sandra Liakopoulos, MD14Tock Han Lim, FRCSEd15Jordi M. Monés, MD, PhD16Sergio Pagliarini, MD, FRCOphth17Daniel Pauleikhoff, MD18Maximilian Pfau, MD19Philip J. Rosenfeld, MD, PhD20David Sarraf, MD21Steffen Schmitz-Valckenberg, MD22Richard F. Spaide, MD23Janet R. Sparrow, PhD24Giovanni Staurenghi, MD25Adnan Tufail, MD26Francesco Viola, MD27Robyn H. Guymer, MBBS, PhD28Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia; Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Australia; Correspondence: Zhichao Wu, BAppSc(Optom), PhD, Centre for Eye Research Australia, Level 7, 32 Gisborne Street, East Melbourne VIC 3002, Australia.Doheny Image Reading and Research Laboratory, Doheny Eye Institute, Pasadena, California; Department of Ophthalmology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CaliforniaDepartment of Ophthalmology, University of Bonn, Bonn, GermanyWisconsin Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WisconsinEye Clinic, Department of Biomedical and Clinical Science “Luigi Sacco”, Sacco Hospital, University of Milan, Milan, ItalyCenter for Public Health, The Queen's University of Belfast, Belfast, United KingdomDivision of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United StatesDepartment of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AlabamaOphthalmic Research Consultants, Waxhaw, North CarolinaDepartment of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UtahVitreous Retina Macula Consultants of New York, New York, New YorkDepartment of Ophthalmology, University of Pennsylvania, Philadelphia, PennsylvaniaDepartment of Ophthalmology, University of Bonn, Bonn, GermanyDepartment of Ophthalmology, Duke University, Durham, North CarolinaCologne Image Reading Center (CIRCL), Faculty of Medicine and University Hospital of Cologne, Department of Ophthalmology, Cologne, Germany; Department of Ophthalmology, University of Frankfurt, Frankfurt, GermanyNational Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, Republic of SingaporeDepartment of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah; Institut de la Mácula and Barcelona Macula Foundation, Centro Médico Teknon, Barcelona, SpainDepartment of Ophthalmology, University Hospitals Coventry & Warwickshire, Coventry, United KingdomDepartment of Ophthalmology, St. Franziskus Hospital, Münster, GermanyDepartment of Ophthalmology, University of Bonn, Bonn, Germany; Department of Ophthalmology, University Hospital Basel, Basel, Switzerland; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, SwitzerlandBascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FloridaStein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CaliforniaDepartment of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UtahVitreous Retina Macula Consultants of New York, New York, New YorkDepartments of Ophthalmology and Pathology and Cell Biology, Columbia University Medical Center, New York, New YorkEye Clinic, Department of Biomedical and Clinical Science “Luigi Sacco”, Sacco Hospital, University of Milan, Milan, ItalyMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomDepartment of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, ItalyCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia; Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, AustraliaPurpose: To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point. Design: A modified Delphi study. Participants: International panel of experts in AMD, retinal imaging, and histopathology that are part of the Classification of Atrophy Meetings group. Methods: A modified Delphi study was undertaken to determine if there is consensus on the acceptability of the onset of end-stage atrophic AMD as a clinical end point to evaluate early interventions and the criteria for defining such an end point. Two initial rounds of online surveys were conducted. Aggregate results and anonymized comments were provided after each round, followed by a face-to-face meeting before a final survey round was completed. Main Outcome Measures: Statements where consensus was reached, defined as ≥80% of responses within the 3-point bracket for agreement or disagreement based on a 9-point Likert rating scale, from a total of 33 statements included in the final round of the survey. Results: Consensus was reached for the statement that the onset of end-stage atrophic AMD was an appropriate clinical end point to evaluate early interventions (82% responses in agreement). Consensus was also reached for the statement that such an end point should be defined based on anatomical changes that have been previously shown in clinical studies to be associated with marked, but not necessarily complete, functional loss (95% responses in agreement). Consensus was nearly reached for the specific criterion that ≥90% of such atrophic AMD lesions should have ≥1 test location that was ≤10 decibels on 2 microperimetry tests (77% responses in agreement). Conclusions: There was expert group consensus that the onset of end-stage atrophy is an appropriate clinical end point to evaluate early interventions in AMD, and that such an end point should show evidence of marked functional loss in prior clinical studies. We believe these findings will help to define incident clinical end points that are acceptable to regulatory authorities. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S2666914525000752Age-related macular degenerationGeographic atrophyDrusenDelphiMicroperimetry |
| spellingShingle | Zhichao Wu, BAppSc(Optom), PhD Srinivas R. Sadda, MD Thomas Ach, MD Barbara A. Blodi, MD Ferdinando Bottoni, MD Usha Chakravarthy, MD, PhD Emily Y. Chew, MD Christine A. Curcio, PhD Frederick L. Ferris, III, MD Monika Fleckenstein, MD K. Bailey Freund, MD Juan E. Grunwald, MD Frank G. Holz, MD Glenn J. Jaffe, MD Sandra Liakopoulos, MD Tock Han Lim, FRCSEd Jordi M. Monés, MD, PhD Sergio Pagliarini, MD, FRCOphth Daniel Pauleikhoff, MD Maximilian Pfau, MD Philip J. Rosenfeld, MD, PhD David Sarraf, MD Steffen Schmitz-Valckenberg, MD Richard F. Spaide, MD Janet R. Sparrow, PhD Giovanni Staurenghi, MD Adnan Tufail, MD Francesco Viola, MD Robyn H. Guymer, MBBS, PhD Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7 Ophthalmology Science Age-related macular degeneration Geographic atrophy Drusen Delphi Microperimetry |
| title | Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7 |
| title_full | Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7 |
| title_fullStr | Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7 |
| title_full_unstemmed | Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7 |
| title_short | Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point—A Delphi Study: Classification of Atrophy Meetings Report 7 |
| title_sort | onset of end stage atrophic age related macular degeneration as an end point a delphi study classification of atrophy meetings report 7 |
| topic | Age-related macular degeneration Geographic atrophy Drusen Delphi Microperimetry |
| url | http://www.sciencedirect.com/science/article/pii/S2666914525000752 |
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